Bridget M. Kuehn

March 15, 2016

CHICAGO — Consensus guidelines designed to reduce methadone-related overdoses in patients being treated for pain are a good starting place for physicians wishing to safely use methadone in palliative care, according to experts.

They spoke as participants of a panel on methadone safety at the Annual Assembly of the American Academy of Hospice and Palliative Medicine (AAHPM) and the Hospice and Palliative Nurses Association (HPNA).

The AAHPM panel presented preliminary guidelines for the safe use of methadone in palliative care.

Methadone has an important role to play in this setting, said one expert.

"For the most part, methadone is a great workhorse drug for the [palliative care] patients we care for," noted panelist James Ray, PharmD, from the University of Iowa College of Pharmacy, in Des Moines. "But you have to be skilled. You have to be vigilant."

You have to be skilled. Dr James Ray

The new consensus guidelines were created in response to an increase in the rate of deaths from methadone overdose that occurred in association with the increase in the use of methadone to treat pain. According to the guidelines, methadone overdoses increased from 900 in 1999 to 5500 in 2007.

More recent data from the US Centers for Disease Control and Prevention suggest that deaths from methadone overdose peaked in 2007, although they continue to account for 1 in 3 opioid-related overdose deaths.

"It is highly implicated in overdose deaths," explained panelist Mary Lynn McPherson, PharmD, of the University of Maryland School of Pharmacy, in Baltimore, Maryland.

She explained that the drug's complex pharmacology is partly to blame. The drug has a long and variable half-life, which can range from 5 to 150 hours. The consensus guidelines say that methadone's half-life usually varies between 15 and 60 hours. As a result, the guidelines recommend slow and careful dosing.

At the meeting, the panelists endorsed many of the recommendations in the consensus guidelines as useful in palliative care, and they provided some additional recommendations on patient selection and monitoring specifically for providers of palliative care.

The AAHPM panel plans to publish a white paper in the next year that will provide more detailed recommendations for the use of methadone in palliative care. Until then, they argued that physicians who employ methadone in palliative care should use the consensus guidelines.

"The [consensus] guidelines are good place to start," said panelist Mellar Davis, MD, of the Hovitz Center for Palliative Medicine at the Taussig Cancer Institute, in Cleveland, Ohio.

Some Specific Recommendations

To create palliative care guidance, the AAHPM panel reviewed consensus guidelines published in 2014 by the American Pain Society (APS) and the College on Problems of Drug Dependence in collaboration with the Heart Rhythm Society in 2014.

The AAHPM group recommends careful monitoring of patients receiving methadone, because the drug has been linked to life-threatening adverse events, including respiratory depression and prolonged QT intervals that can lead to sudden death.

Caregivers should check the patient several times a day for signs of sedation, Dr McPherson said. "You get sedation before you have respiratory depression," she explained.

The AAHPM panel endorsed the consensus recommendations that patients with risk factors for QT prolongation receive a baseline ECG prior to the initiation of methadone and that a baseline ECG be considered even for patients without risk factors. The guidelines recommend use of an alternative drug if the patient's QT interval is higher than 500 ms. Ongoing monitoring is recommended during treatment.

Emerging evidence has begun to identify genetic variants that may contribute to a patient's having either slow or fast methadone metabolism, noted Dr Ray.

"If you don't know [the patient's] pharmacogenetics, you could get in a lot of trouble [with aggressive dosing]," he said. "I would dose conservatively."

Dr Ray explained that methadone also has many drug interactions that must be taken into consideration when determining dosing. Cytochrome P450 enzymes metabolize methadone, and a myriad of drugs can either decrease the activity of these enzymes, thereby boosting methadone levels, or increase methadone metabolism, thereby lowering methadone drug levels, according to the consensus guidelines. Because of this, physicians must consider how starting or stopping any drug will affect methadone metabolism in a patient.

"Methadone, of any drugs we work with, has the longest list of drug interactions," Dr Ray said.

The degree of patient monitoring should be adjusted in accordance with on the goals of the patient's care, Dr Davis said.

"If they are being treated, we would tend to adopt the [consensus] guidelines from APS," Dr Davis said. "In hospice, we don't really expect as much monitoring, because they have a short time. It's really a more of symptom management process [in hospice]."

The panel also recommended careful patient selection. Because it can take a long time to properly adjust the methadone dose, patients whose life expectancy is 1 week or less are not good candidates for methadone therapy, Dr Ray said. It is also not advisable for patients whose caregivers are less skilled, because they may be unable to monitor treatment appropriately, he said. Caregivers and patients with a history of substance abuse must also be carefully assessed, Dr Ray said.

Dr Davis noted that patients may abuse the drug or divert it, so it is important for physicians to be vigilant for signs of abuse and to set clear expectations with patients.

"Be careful who you give this to," Dr Davis said.

Patients in palliative care and their caregivers also must be educated about the safe use of the drug, including what adverse effects to watch for and what to do if they occur, Dr Davis said.

"A lot of education goes into using methadone with patients," Dr Davis said.

The panelists have disclosed no relevant financial relationships.

Annual Assembly of the American Academy of Hospice and Palliative Medicine (AAHPM) and the Hospice and Palliative Nurses Association (HPNA): Abstract FR439, presented March 11, 2016.


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